Abstract 4002: Adipose tissue supernatant of overweight ER positive breast cancer patients promotes migration of MCF-7 breast cancer cells

Abstract

Abstract Introduction: Adipose tissue is a major component of the breast cancer microenvironment, and preclinical studies have suggested that adipose tissue might play a pivotal role in breast cancer progression. In this study we investigated the effect of adipose tissue from patients with ER positive breast cancer on migration of ER positive MCF-7 breast cancer cells. Materials and Methods: Adipose tissue samples were collected from patients with ER positive breast cancer undergoing a mastectomy. In total, adipose tissue samples from 3 normal weight (BMI: 18.5-24.9) and 7 overweight breast cancer patients (BMI: 25-29.9) were collected. Samples from the mastectomy specimens were minced in small pieces, incubated in RPMI-1640 and after 48 hours (h) the supernatant was harvested. The effect of adipose tissue supernatant on the migration of MCF-7 cells was monitored in real-time for 48 h with the xCELLigence cell invasion and migration plates expressed in delta cell index (DCI). In addition, effect of adipose tissue supernatant on migration was assessed by quantification of F-actin positive lamellipodia of MCF-7 cells in a scratch assay after 24 h. In all experiments, RPMI-1640 with 1% or 20% FCS was used as a negative or positive control respectively. Results: Supernatant of overweight patients significantly induced MCF-7 migration compared to supernatant of normal weight patients after 24 h (xCELLigence DCI: 1.22 ± 0.15 vs. 0.95 ± 0.19 (P=0.038)), 36 h (DCI 1.40 ± 0.21 vs. 0.91 ± 0.31 (P=0.019)) and 48 h (DCI 1.72 ± 0.23 vs. 0.98 ± 0.43 (P=0.007)). In addition, there was a significant difference between the overweight group and negative control at 36 h, and 48 h (DCI 1.40 ± 0.21 vs. 1.06 ± 0.12, P=0.038 and DCI 1.72 ± 0.23 vs. 1.11 ± 0.21, P=0.004 respectively). No significant difference between normal weight group and negative control was found at any of the time points. After 24 h MCF-7 cells incubated with supernatant of overweight patients developed significantly more F-actin positive lamellipodia compared to MCF-7 cells incubated with supernatant of normal weight patients (44.26 ± 3.26% vs. 25.47 ± 1.88% P<0.001). Conclusion: In this study, we showed that adipose tissue supernatant of patients with ER positive breast cancer can promote migration of MCF-7 breast cancer cells in a weight dependent manner. Whether this is the case in other breast cancer subtypes as well, and the potential clinical implication, is of interest for future studies. Citation Format: Jie Ma, Hetty Timmer-Bosscha, Paul M. Werker, Carolina P. Schröder, Marlous Arjaans. Adipose tissue supernatant of overweight ER positive breast cancer patients promotes migration of MCF-7 breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4002.